An enzymatic approach was developed to study the solution structure of the transcription factor MAX - a member of the basic-helix-loop-helix zipper family of DNA-binding proteins. This approach involves a proteolytic protection assay of the Max protein both in the absence and presence of DNA. The assay is based on the notion that residues of the protein, which are either buried or within regions of structural rigidity, will exhibit protection against proteolysis. In contrast, solvent exposed and flexible regions of the protein will be less protected. The assay uses matrix-assisted laser desorption ionization mass spectrometry to map rapidly and accurately the sites of proteolytic cleavage with HPLC. The work has resulted in a host of new findings, culminating in the publication of a full-length report in the journal Protein Science. A computer-designed figure from the paper was accorded the cover of the journal.